THE USE OF MOIST WOUND HEALING WITH INFECTION

THE USE OF MOIST WOUND HEALING WITH INFECTION CONTROL IN THE BURN WOUND
AUTHORS: Robert H. Demling, M.D. Leslie DeSanti R.N., .
TABLE OF CONTENTS
Section 1
Moist Wound Healing (current concepts)
Section 2
Current Management of the Burn Wound:
Use of antibacterial agents and skin substitutes
Section 3
Moist Wound Healing with Sulfamylon Solution for the Burn
Wound
Section 4
References
1
SECTION I. MOIST WOUND HEALING (CURRENT CONCEPTS)
A. HISTORICAL OVERVIEW
Prior to the late 20th century, wounds were felt to heal better if exposed under a "scab". This process produced surface
desiccation and eschar formation now known to deepen the wound, but was thought to protect the wound. The thinking
may have been correct given the fact that no antibacterial agents were available to treat an infection.
The most detailed descriptions were found in medical books from Ancient Greece. Although the initial ingredients first
applied to the burn and other wounds varied considerably, wound dryness was always sought.
The description of the healing process leading to scar as the normal endpoint would indicate that outcomes were less
than ideal.
This concept remained popular for wound care until the mid-20th century (and even longer for the burn wound). One
exception was a report in the early 19th century where burns and wounds were managed with the wound immersed under
water, with good healing results. This concept was not accepted however as a standard of care.
•
•
•
•
•
Copeland
Sneve
John
Davidson
Wallace
1897
1905
1910
1925
1947
open and exposed
open and exposed
open method
tannic acid to producing an eschar
Exposure
Allen and Koch in 1942 popularized a petrolatum gauze and dressing closure method, which decreased the surface
drying. The primary death from burns was at that time and remained so, septicemia from burn infection and therefore
there were many who returned to exposure, especially with the advent of a topical antibiotic cream by Fox 1969 (silver
sulfadiazine) and Moncrief 1971 (sulfamylon). The introduction of silver nitrate soaks by Moyer in 1965 required an
occlusive dressing and was the first use of a moist wound healing method in burns. However, the main concept in burn
care was not wet or dry, but rather control of infection by topical antibiotics.
•
•
•
Moyer
Fox
Moncrief
1965
1969
1971
-0.5% silver nitrate solution
-silver sulfadiazine
-sulfamylon
These topical antibiotics can control infection but do also retard healing, especially re-epithelialization.
The following diagram describes the interesting conceptual diversion of non-burn wound, burn wound care in the 1960’s
as to optimum management when moist wound healing was popularized. This difference in management persists today.
However the availability of a sulfamylon solution may alter this approach.
Ancient Times to
Mid
1960’s
Exposure
method
with surface scab
Not Moist Healing
1960’s
2
Advantages of moist healing defined
Different approach used for wounds vs burns
1960’s to present
Diverse Wounds vs. Burns
Non-Burn Wounds
Burn Wounds
Moist Wound Healing
Superficial
Deep
Non-Infected
Clean
Moist Healing
Alone
Add Debridement
to Moist Healing
Not Moist Healing
Deep burn
NonInfected
or
Infection
Present
Superficial
Burn
Topical antibiotic cream
Occlusive gauze
Used until healed
If infection present
Not moist
healing
or
Moist healing
with skin
substitute
Excision and grafting
•
•
•
Moist Healing plus a local
antibiotic
Systemic antibiotics
Debridement
Moist healing begins
• Antibiotic solution
• Biologic dressing
• Skin substitute
3
Example of exposure approach with dry eschar
This approach is now recognized to retard the healing process
4
B. PROPERTIES OF MOIST WOUND HEALING
A landmark study in 1962 by Winter demonstrated that partial thickness wounds re-epithelialized more rapidly under
occlusive dressings with the reason being that occlusive dressings maintained a moist wound surface. This environment
accelerated the re-epithelialization process. Numerous studies followed which demonstrated that wound occlusion and
moisture increased all phases of healing. Wound bacterial colonization that can occur in a moist healing environment
does not appear to retard healing or cause sepsis. However, wound infection, as expected, did decrease the healing
process, the difference between colonization and infection being the quantity of bacteria. Colonization is defined as less
than 104 bacteria/gram of tissue and infection being over 105 bacteria/gram. The data, demonstrating that a moist wound
surface increases re-epithelialization and all other components of wound healing, is now well established. Any surface
desiccation leads to both an increase in wound depth and infection.
Problems of Surface Desiccation
•
•
•
•
•
Increased depth of surface tissue necrosis
Impediment to surface epithelial cell migration
Decreased surface oxygen available for healing and bacterial killing
Impairs nutrient flow to surface
Increases infection risk
Non-Burn Wounds
•
•
•
•
Moist wound care improves healing 1962
Increasing use of occlusive dressings mainly for partial thickness wounds 1970
Development of occlusive dressing to decrease wound surface water vapor loss (WVTR): hydrocolloids, films, etc.
1970’s to present
Universal acceptance of maintaining moist wound healing environment for wounds
Surface drying not only impedes delivery of nutrients and immune defenses to the wound surface but also markedly
impedes the ability of cells to migrate across the wound surface. Epithelial cells need a moisture layer to migrate and
spread. For any re-epithelialization to occur on a dry surface, the cells must burrow beneath the "scab" using a controlled
release of proteases.
Moisture is required for:
•
•
•
•
Activity of growth factors
Activity of surface proteolytic enzymes
Surface oxygen delivery
More effective nutrient delivery
The optimum approach to maintaining a moist wound surface is the use of occlusive dressings. These dressings include
polyurethane films, a variety of hydrocolloids and an increasing use of adherent synthetic skin substitutes such as
Biobrane.
5
Advantage of a Moist Wound Surface
•
•
•
•
•
•
Reduction in wound surface conversion
Decrease in surface desiccation and eschar formation
Increase in local growth factor production
Enhanced wound surface immune defenses
Increased rate of angiogenesis and fibroblast proliferation
Increased proliferation and migration of epithelial cells along thin water layer
Comparison of Maintaining Moist Surface Versus Open Wound
•
•
•
•
Moisture increases re-epithelialization by 30-50%
Moisture increases collagen synthesis by 5-%
Rate of re-epithelialization with moisture 2-5 times faster
Marked decrease in wound surface fluid loss
Surface desiccation results in impairment to rate of re-epithelialization and decreases all phases of healing
Moisture layer accentuates wound closure
6
Characteristics of Moist Wound Healing for Partial Thickening Injury:
(Surface Moisture Layer Maintained)
•
•
Rapid movement of epithelial cells across surface
Decreased surface inflammation
A marker of the moisture retention on the wound surface has been the Water Vapor Transmission Rate thru the dressing
(WVTR in g/m2/hr). The lower the WVTR, the more effective the dressing or skin substitute is at maintaining wound
surface moisture.
WVTR 35g/m /hr is as defined as moisture retentive
Lower WVTR Correlation
•
•
•
Predictor of more rapid healing
Predictor more rapid re-epithelialization
Predictor more rapid wound contraction
C. WOUND MOISTURE DOES NOT INCREASE POTENTIAL WOUND COMPLICATIONS
Infection or at least wound colonization has been considered to be a potential complication, especially in a burn. However,
on a clean wound, moisture minimizes wound progression to non-viable tissue. Injured tissue will increase organism
growth as in the presence of non-viable tissue or eschar on a mid to deep partial or full thickness non-burn wound.
Antibacterial creams are still the mainstay in deep burns even though desiccation and increased exudation and decreased
healing will likely occur. However a solution with antibacterial properties can control infection and maintain moist healing.
Problems of Wound Infection
•
•
•
•
Impaired local healing
Potential for sepsis
Increased local exudates and inflammation which can lead to chronic wound
More concern in a burn than in a non-burn wound
7
Decrease in Wound Pain
•
•
Moisture retentive dressings
Temporary skin substitutes
2) Pain:
Pain is a major complication of wound care. Removal of a dry dressing on a partial thickness wound results in much
greater pain than removal or change of a moist dressing.
Moisture-retentive dressings (or adherence skin substitutes left in place) cause less pain.
3) Skin Maceration:
The concern over moisture and skin maceration relates mainly to exudates, which in increased amounts will lead to tissue
maceration. Wounds, moist or even wet with a solution (where exudates is absorbed or removed) have been shown to
actually increase healing rate.
4) Hyper granulation:
Hyper granulation is a complication of excess granulation tissue occurring in a full thickness wound. This complication has
been prevalent well before the use of a moist wound environment and therefore moisture is not the cause.
Recent studies in acute wounds have indicated decreased inflammation and less granulation tissue using moist healing.
Are There Complications with Moist Wound Healing?
•
Infection?
-does not appear to be increased in a clean wound, even with non-viable tissue on the surface
•
Skin Maceration?
-does not appear to occur unless exudates is allowed to accumulate
•
Hypergranulation
-seems to be less with moist healing as surface inflammation is decreased
•
Pain?
-Pain is less with this method
Section II. CURRENT MANAGEMENT OF THE BURN WOUND (USE OF ANTIBACTERIAL AGENTS AND
TEMPORARY SKIN SUBSTITUTES)
A. AN OVERVIEW OF THE BURN WOUND
The burn eschar (non-viable tissue) is still considered to be not only at high risk for infection, but also to contain toxins,
e.g. oxidants, cytokines that can produce systemic dysfunction.
The major change in burn wound management over the past 40 years has been a more rapid removal of devitalized
tissue (eschar) and earlier wound closure. However, the perception that an uninfected eschar requires an antibacterial
cream (solution) to control infection until eschar removal persists. This concept includes not only deep burns to be
excised, but also mid-dermal burns, which are managed with a topical cream until the eschar has been removed and reepithelialization has occurred.
8
The concepts of optimum burn wound management remained focused on avoiding wound infection first with topical
antibiotics and more recently early excision and grafting. Infection has been a much greater concern for the deep burn
wound likely due to the combination of impaired local immunity, with the presence of dead tissue, and impaired systemic
immunity with a large injury.
The role of moist wound healing has now been recently adopted for the more superficial burn, skin grafts (mainly meshed
grafts) and for a clean excised wound. (awaiting a graft). Moist healing can be provided with temporary skin substitutes in
the superficial burn and use of an antibiotic solution in the deeper burn.
The current approach to the deep burn is the use of antibacterial agents till excision or healing. Surface desiccation using
this approach is common as topical creams are hyperosmolar. Also, these cream based topical agents can retard healing.
Burn Wounds
•
•
•
•
•
Topical antibiotic creams are commonly used with eschar present
Creams can lead to desiccation
Recent switch for superficial burns, meshed skin grafts, excised burns to moist wound healing
Infection remains a greater concern for the burn than the non-burn wound
Antibacterial solutions and moist healing have a positive role in burn care
Mid-Dermal Burn
Common use of a topical cream plus an occlusive dressing
Use of a Topical Antibiotic Cream to Treat Infection
Advantage
• Penetrates burn eschar, especially suylfamylon
• Controls bacterial growth
• Improves healing by controlling infection
Disadvantages
• Does not provide optimum healing environment
• Negative effects on the healing process unrelated to infection
• Often treating colonization, not infection
9
B. CURRENT APPROACH TO BURN CARE
1) The Superficial Burn
The superficial burn is confined to the upper third of the dermis leaving a good blood supply and lots of remaining
epidermal cells for re-epithelialization. The current approach is to use an occlusive dressing, e.g. xeroform gauze which
then dries out
Legend: The area of coagulation has been completely removed, exposing a viable but injured wound surface (zone of
injury), which can deepen. The surface itself has an increased content of fibrin produced by activation of the clotting
cascade and fibronectin produced by the dermal cells. There is also evidence of the onset of inflammation with
vasodilatation, increased neutrophils, and macrophages. The wound surface also has increased proteolytic activity, which
if persistent, can denature new tissue formation and growth factors.
Typical Superficial Burn Wound
Ready to be occluded
10
Superficial wound left open
Exudate is beginning to build up at 2 hrs, if not closed. Wound not infected.
Superficial Burn Wound
Treatment with grease gauze, which then dries on the surface. This approach is not moist healing.
Treatment with Moist Healing Using a Temporary Skin
Use of a temporary skin substitute will adhere to the surface while maintaining a moisture layer on the
wound surface to optimize healing.
11
Superficial Burn Covered with Skin Substitute
A temporary skin substitute adheres to the wound surface and maintains the surface moisture layer
optimizing re-epithelialization.
Close with Temporary Skin Substitute
The temporary skin substitute (Biobrane) adheres to the
partial thickness wound. Note moisture layer is maintained on
the surface. No antibacterial is needed.
2) Mid to Deep Dermal Burn
The most common approach is to use a topical antibacterial
cream with fine mesh gauze covered with a dry occlusive
dressing once or twice daily. However, this approach does
not produce the optimum-healing environment as surface
desiccation can occur as well as increased inflammation.
12
A schema of mid-dermal wound is shown, treated with topical antibiotics. A pseudo-eschar forms on the surface from
wound exudates, protein, and antibiotic cream. This surface inflammation can lead to further tissue damage, causing a
portion of the zone of injury to convert. In addition, increased wound protease and mediator activity can decrease the
normal healing process.
A topical antibiotic solution such as 5% sulfamylon solution would decrease the surface exudates while maintaining
moisture and infection control under a secondary dressing.
3) The Full Thickness Burn
The most common approach to care is the use of a topical antibiotic cream until excision and grafting.
DEEP BURN
A topical cream needs to be in this case, mafenide cream due to increased penetration properties.
A topical antibiotic solution, 5% sulfamylon solution, would penetrate the eschar; decrease the surface exudates while
maintaining moisture and infection control.
C) THE EXCISED AND GRAFTED BURN WOUND
1) The excised wound
As the burn is a contaminated wound, some bacteria will be present on the excised wound surface prior to skin graft
placement. If the wound is not immediately grafted the surface must be protected from desiccation and infection. A moist
wound surface layer needs to be maintained.
Temporarily Covering the Excised Wound
• Use of temporary skin substitute
• Use of an antibiotic solution
The choice often depends on how clean the wound is, as a temporary skin substitute does not have an antibiotic properly.
Although the adherent nature of a skin substitute maintaining surface moisture does improve the local immune defenses
13
The Excised Wound
Fat and remaining dermis are exposed.
If grafting is not immediate then wound protection against desiccation and _____
14
Excised Wound Covered with Temporary Skin Substitute
Biobrane applied immediately. Note protected wound one day later with excellent adherence and maintenance of surface
moisture. Area of overlap about to be removed.
Previously Exposed Wound
Biobrane is removed and skin grafting to follow.
Note wound vascularity has been maintained and actually improved.
Excised wound treated with antibiotic solution
15
Wound surface moisture is being maintained as is infection control by injection of 5% sulfamylon solution through the
burned catheters
2) The Meshed Skin Graft
The use of an occlusive dressing and an antibiotic solution to maintain surface moisture is now a common approach to
management of the meshed skin graft (or excised wound)
The most common current approach is to use the moist wound healing techniques using a topical antibiotic solution
beneath an occlusive dressing.
Common Antibiotic Solution
*5% sulfamylon solution has been shown to a more effective antibacterial solution
and to also not retard healing
16
Section IV. MOIST WOUND HEALING WITH SULFAMYLON SOLUTION
There appears to be a difference in infection risk between the burn and non-burn wound. Topical antibiotic coverage for
burns with surface non-viable tissue would appear to be justifiable given the historical risk of infection.
A Novel Antibacterial Solution (The Properties of 5% Sulfamylon Solution)
Sulfamylon: also known as Mafenide acetate is a white crystalline powder freely soluble in water. It was developed as a
powder, a solution, and a cream and first studied for clinical use in 1940 for prevention of gangrene in war injuries. The
product was first used in burns as a cream and was found to have excellent antibacterial properties and penetration into
devitalized tissue.
HISTORY
•
•
•
•
•
•
•
•
Studied and used in World War II in the powdered form to control infections
Studied in 1960’s in 5% and 20% solution to treat clostridia infections
Studied in 1960’s in burns as a cream to control pseudomonas
Used clinically as a cream in burns in 1960’s
Marked decrease in invasive wound infection
Widespread use of cream decreased with development of silver sulfadiazine in 1970’s which had fewer acid base
problems and less pain
Continued use of 5% sulfamylon solution for meshed skin grafts and in some centers for deep burns to the
present time.
Late 1990’s – FDA approved use of the solution for control of infection in meshed skin grafts or excised wounds.
The complications of pain on application of sulfamylon cream and the side effects of carbonic anhydrate inhibition, leading
to metabolic acidosis, led to a decrease in its use with the development of silver sulfadiazine. However, its use as a 5%
solution continued in a number of major burn centers for use on wide meshed skin grafts and excised wounds to protect
against potential post-graft infection as well as on deep dermal burns. The 5% sulfamylon solution has been FDA
approved for use on meshed grafts and excised burn wounds) The solution is isosmolar compared to the very
hyperosmolar sulfamylon cream.
Mechanism of Action: Sulfamylon has bacteriostatic action against many gram positive and gram-negative organisms
including Pseudomonas aeruginosa but is not active against fungi. The solution penetrates thru eschar as effectively as
the cream form. Once absorbed systemically, the compound is rapidly converted to an inactive metabolite and cleared
thru the kidneys. The product is completely cleared from the body 24 hours after an application.
Complications of Sulfamylon Solutions
Rash = 4% (comparable to other topical antibiotic solutions)
Metabolic Acidosis – very uncommon
Pain – mild (much less than use of cream)
Fungal growth – can selected out for fungi
17
Characteristics of 5% Sulfamylon Solution
•
•
•
•
•
•
•
•
•
Osmolarity 240mg m osm/kg which maintains isomolar wound fluid environment
Minimal pain on application
Less than 6% incidence of any metabolic acidosis
Found not to be toxic to human keratinocytes on human skin
Penetrates eschar to a comparable degree to sulfamylon cream
Broad bacteriostatic action against most gram negative and gram positive micro-organisms especially
Pseudomonas
Incidence of skin rash (4%) comparable or less than neomycin, Polymyxin solution
Can add nystatin to cover fungi
Stable in solution, once mixed, for over 16 weeks
1) Antibacterial Properties
Treatment of Infected Burn Wound
(Comparison of 5% Sulfamylon Solution with Other Agents
as effective as Sulfamylon cream and more effective than Silver Sulfadiazine at the 144 hr post burn time period (J Burn Care R
n shown to be effective in both preventing and in treating burn wound infections.
18
2) Penetration of Sulfamylon Solution
Burn Tissue Concentration of Sulfamylon
( 5% Solution vs. 11% Cream)
•
5% Sulfamylon solution penetrates devitalized tissue better than the cream base sulfamylon
hown to have excellent eschar penetration. In fact, the solution appears to be more effective than the cream base.
19
3) Effect of Sulfamylon Solution in Re-epithelialization
Conclusion: Sulfamylon solution does not retard epithelialization on a clean wound compared to saline and significantly
increases epithelialization rate of a contaminated mesh graft by control of surface bacteria. (Burns 1999-25; 237)
20
4) Use of 5% Sulfamylon (Mafenide) Solution in Burns
Reported side effects as % of total use
(J Burn Care Rehab 1993:14; 158) (J Burn Care Rehab 1988:9; 602)
dence of metabolic-acidosis and of pain on application is extremely low with sulfamylon solution compared to the cream. The
e of a skin rash is 10-15% for both cream and solution. The addition of nystatin to this solution can decrease the incidence of fu
wth.
21
5) Maintaining Moisture of Surface
Comparison of Neo-eschar Formation and Surface Desiccation
5% Solution versus Cream
The high osmolarity of a cream base removes surface moisture causing a neo-eschar.
The 5% solution is isomolar leading to a moist surface.
(J Trauma 1983:23; 878)
22
6) Sulfamylon Solution: Pain on Application.
Comparison of Pain from Sulfamylon Products
(5 % Solution vs. 11% Cream)
There is minimal pain with use of the solution
( Arch Surg. 1975:110; 1446) (J Trauma 1983:23; 878)
Use of 5% Sulfamylon Solutions
•
•
•
•
•
•
•
Mix Sulfamylon powder product into sterile water or saline
Filter solution through filter provided
Store at room temperature
Cover wound surface – fine mesh – then an inner wet and outer dry gauze
Apply solution to inner layer of 8 ply gauze – covered with an outer layer of dry gauze best done through irrigating
catheters between the layers every 6-8 hours
Keep inner gauze near wound surface moist
Can maintain dressing in place for 5 days (if exudates minimal)
23
C) Other Antibiotic Solutions for Burn
1) Neomycin Sulfate is bactericidal in action being effective against gram-negative organisms but not effective against
Pseudomonas. It has not been found to penetrate devitalized tissue and is therefore used on clean wound surfaces to
control bacterial growth. The usual concentration for topical use is 0.1 to 0.2%.
Characteristics of 0.1% Neomycin Solution
•
•
•
•
•
•
•
•
Broad spectrum antibacterial coverage mainly gram negative except for pseudomonas
No effect on fungi
Non-toxic to tissue growth
Does not penetrate devitalized t6issue
Skin sensitivity seen 5-15% of patients
Can add nystatin to control surface fungi
Not painful on application
Long shelf life – stable in solution
2) Polymyxin B Sulfate occurs as a powder, which readily dissolves in solution. Polymyxin B is bactericidal for most gramnegative species but has no gram-positive organism or fungal activity. It is non-toxic to tissues and skin sensitivity is rare.
Polymyxin B Solution
•
•
•
•
•
•
Bactericidal for most gram negative organisms
Not effective against gram positive organisms or fungi
Not toxic to wounds
Not painful on application
Rare skin sensitivity
Stable in solution if protected from light
3) Bacitracin is a polypeptide bacteriostatic antibiotic active against many gram-positive organisms, but not against gramnegative organisms or fungi. Bacitracin is precipitated from solution by any heavy metals. It does not penetrate tissue and
is not toxic when applied topically. Skin sensitivity is rare.
•
•
•
•
Bacteriostatic against gram positive organisms
Not effective against gram negative organisms or fungi
Not toxic to wounds
Not painful on application
Often combinations of Bacitracin and neomycin are used to increase antibacterial Properties. Nystatin an anti-fungal can
also be added.
•
•
•
Dissolve powders in solution to appropriate concentrations
Apply to wound surfaces usually on 8 ply gauze covering fine mesh with dry gauze overlay
Can use irrigation method to decrease dressing changes and maintain wound moisture layer
D) Comparison of Antibacterial Safety and Stability Properties of Neomycin, Neosporin, Polymyxin and Sulfamylon
Solutions on Wounds.
A comparison of 5% Sulfamylon Solution with Double Antibiotic Solution for Grafts in Burns. Warden GD, MD, et al.
Shriners Hospitals for Children, Cincinnati, OH
June 1998 marked the approval of Sulfamylon (mafenide acetate) 5% solution (SMS) by the FDA. This was preceded by
many years of clinical use for microbial control in excised and grafted burn wounds under an Investigational New Drug
exemption.
24
The SMS IND study prospectively included those patients with large burns (28.9% Total Body Surface Area – TBSA),
burns with known Pseudomonas colonization and burns exposed to the flora of other burn units. These patients were
treated with SMS alternating with Double Antibiotic solution (DAB: Neomycin 40mg. + Polymyxin B 200,000 U/I) to fresh
skin grafts. Smaller burns (9.7% TBSA) whose grafts were treated with DAB alone were evaluated retrospectively for
comparison. 438 patients were treated between 5/21/91 and 10/13/95; including 281 in the SMS/DAB (study) group and
157 in the DAB only (control) group.
Treatment failure was defined as infectious graft loss or a change in topical treatment due to colonization with the
potential for loss. Within the two treatment groups 11 DAB and 44 SMS patients had graft loss. These losses were
significantly less in the SMS group by the Cochran-Mantel-Haenzel Boot Strap estimation of Odds Ratio, despite the fact
that this group had significantly larger burns. A change in topical treatment was required for 7.6% of the DAB patients, but
only 2% of the SMS patients.
The cause for change in the latter group was generally the need to cover yeast or fungus. Microbial prevalence within
each group was significantly different (p = 0.001) in the growth of any organism at day 5, with 76% of the DAB group
having positive cultures versus only 54% of the SMS group. There were more positive cultures for Staph (p = 0.05) and
Pseudomonas aeruginosa (p < 0.001) in the DAB group at day 5 than in the SMS group. Day 10 was significant for
positive cultures in the DAB group (p=0.001). Gram-negative organisms were also significantly higher in the DAB group at
both day 5 (p< 0.001) and day 10 (p=0.001). Yeast and fungus were not controlled well by SMS in the very large burns.
Significantly more yeast grew in the SMS group at day 2 (p=0.011) and day 5 (p< 0.001). Fungal growth was higher in the
SMS group at days 2,5 and 10. In summary, this study was clearly biased against SMS with a larger burn size and higher
mortality in this group. Despite the larger burns.
SMS reduced the infectious graft loss compared to DAB.
(J Burn Care Rehab 1999:20; 232)
25
The Efficacy of Combining Neosporin GU Irrigant and Nystatin as a Burn Wound Antimicrobial Dressing Change P, MD, et
al. The University of Iowa Hospitals and Clinics and College of Pharmacy, Iowa City, IA
Introduction: In an attempt to alternate topical agents and to individualize their use to specific burn wounds, Neosporin
G.U. Irrigant is sometimes used as a wet dressing for second and third degree burn wounds. This study was designed to
evaluate the combination of this solution with Nystatin to increase the broad-spectrum coverage of the Neosporin to
include antifungal activity.
Methodology: ATCC stock cultures and 2 burn wound isolates of each species of common burn wound pathogens were
tested for antimicrobial susceptibility or resistance against 4 different concentrations of Nystatin (50,100, 150 and 200
units/ml) combined with Neosporin GU Irrigant. The antimicrobial activity was determined using the Holder Wet Disc
Antimicrobial Solution Assay. Sterility was confirmed by broth culture.
Conclusion: Neosporin and nystatin can be combined and used as a burn wound dressing with antifungal activity with
nystatin concentrations of 150 units/ml or more. Neosporin GU solution is not effective against Pseudomonas
Enterococcus and Proteus mirabilis. However, this combination can broaden the spectrum of activity as a burn wound
dressing for common skin flora (J Burn Care Rehab 1999:20:232.)
26
The Efficacy of Topical Sulfamylon 5% Solution with Selected Topical, Oral, and Parenteral Antifungals In Vitro, P Muller,
PA-C, M, Stafford, Pharm D, J Hansbrough, MD.
University of California, San Diego Medical Center, San Diego, CA
Sulfamylon (mafenide acetate 5%, Bertek, Inc) is often used with antifungal agents to enhance coverage of Candida,
Aspergillus and other fungi. There are conflicting reports on the efficacy of these drug combinations. We studied efficacy
of 5% Mafenide acetate solution (MAF) with topical miconazole and nystatin, and systemic antifungal agents including
amphotericin B (AMPHB), itraconazole and fluconazole in vitro.
Methods: MAF was combined with Micro-Guard (miconazole nitrate 2%) and Nystop (nystatin 100K USP U/gm) powders
at standard concentration, 1:10 and 1:100 dilutions and plated on ATCC C albicans and B subtilis. Zones of inhibition
were measured at 24 and 48 hrs and compared with standards for each agent alone. Effects of 5%, 0.5% and 0.05% MAF
on systemic antifungal agents were measured by sensitivity testing. Post controls were diluted to appropriate known
tissue achievable levels. 2-fold dilutions of itraconazole and AMPHB were tested in presence of ATCCC albicans and 2 pt
isolates of Aspergillus fumigatus.
Results: In the bioassay, the zones of inhibition test for antagonism when combining MAF with chemical and commercial
grade nystatin and miconazole powders. Small diameter sizes indicate antagonism, and larger zones correlate with
synergism. Equal diameter sizes indicate no effect. Combinations of MAF with miconazole and nystatin powders showed
no clinically significant difference in zone sizes when tested against both B subtilis and C albicans. Although nystatin;
MAF combination decreased zone age against C albicans, this was most likely related to poor solubility. In addition, the
antibiotic sensitivity testing checked for antagonism by MAF on antifungal activity of miconazole, fluconazole,
itraconazole, and AMPHB. MAF had no effect on activity of AMPHB and itranazole and AMPHB. MAF did not effect
activity of AMPHB and itraconazole, and AMPHB. MAF did not affect activity of AMPHB and itraconazole toward ATCCC
albicans and 2 pt isolates of A fumigatus. MAF increased MIC of fluconazole against ATCCC albicans from 0.25 to 0.5
mcg/ml, but these levels remained well below typical MIC’s of the organism.
Conclusion: MAF and selected antifungal agents showed no antagonism when combined. Our results may differ from
previous studies because we used a powder formulation of nystatin; we suspect its sparingly soluble nature levels low
amounts of drug in solution to yield activity against C albicans.
We recommend MAF 5% solution with miconazole powder for broad topical coverage of burn wounds. (J Burn Care
Rehab 2000:21; 215)
27
Safety of 5% Sulfamylon Solution Irrigation Used after Skin Grafting
W.R. Dougherty, MD
LAC & USC Medical Center, Los Angeles, CA
Introduction: Sulfamylon solution 5% (SS) has been used as an adjunct to wound care after skin grafting for many years
prior to its approval by the FDA for routine use. This is a summary of an IRB/FDA approved study of the safety of SS
conducted in our burn center.
Methods: SS was used as a post-graft irrigant after Institutional Review Board approval to treat burn patients who
underwent tangential excision and skin grafting. Records of this study were reviewed to assess safety. Via irrigation
catheters placed at surgery, dressings were kept moist with SS solution until graft take and the interstices were closed.
Nystatin Powder (10,000 u/ml) was added for fungal prophylaxis. The records of this study and recorded complications
were resolved.
Conclusions: Utilizing a strict post graft wound care protocol, 5% Sulfamylon solution has a low complication rate as an
adjunct to surgical debridement and grafting after burn injury. SS provides a moist antibacterial wound environment during
and should be considered for wounds with a significant risk of wound infection. (J Burn Care Rehab 2000:21; 214.)
28
Potency and Stability of Neosporin as a Burn Wound Antimicrobial Over Prolonged Storage Time
Rosenquist MD, MS, MT, Kealey GP, MD.
University of Iowa College of Medicine Department of Surgery, Iowa City, IZ
The development of sophisticated antimicrobials has revolutionized burn care. In an attempt to alternate topical agents
and individualize their use to specific burn wounds, a study using Neosporin GU irrigant (NGUI) in topical wound therapy
was undertaken. Some issues raised in considering Neosporin were storage temperature and solution outdate. The
purpose of this study was to assess the potency and stability of NGUI over time and at varied storage temperatures.
ATCC stock cultures of Pseudomonas aeruginosa (PSA), Escherichia coli, Enterococcus faecalis, Enterobacter cloacae,
Staphylococcus aureus (HAS), Methicilllin Resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermis and
2 burn wound isolates of each species were tested for antimicrobial susceptibility/resistance and sterility over 16 weeks.
The antimicrobial activity was determined using the Holder Wet Disc Antimicrobial Solution Assay. Sterility was confirmed
by brother culture and testing was done weekly. The antibiotic solution was prepared in the manner and concentration
used in clinical wound care and stored at 37, 25 and 4° C.
Sterility for all test solutions was maintained using standard laboratory sterile technique for the length of the study.
Antimicrobial activity remained constant from strain to strain. Individual strain sensitivity patterns remained the same
throughout the study. At 16 weeks the zones of inhibition had not changed and decreased potency was not noted. All
isolates of Staphylococcus epidermis, Staphylococcus aureus, MRSA, Escherichia coli, and Enterobacter cloacae were
sensitive to NGUI; while isolates of PSA and E. faecalis were resistant to NGUL. Storage temperature did not affect
potency. In conclusion, NGUI is a cost effective topical that can be used on the same patient after opening the container
as long as sterile technique is used. NGUI maintains its efficacy and stability in storage where in an incubator, on the
shelf, or in a refrigerator for a minimum period of 16 weeks. Proceed Amer Burn Assoc 1996:173;
29
Stability and Potency of 5% Mafenide Acetate Suspension Over Time
Rosenquist MD, MS, MT (ASCP), Lewis II RW, PA-C, Kealey GP, MD
University of Iowa College of Medicine Department of Surgery, Iowa City, IA
Topical 5% Mafenide acetate suspension (MAS) has been shown to be effective in controlling microbial growth in the
treatment of burn wounds. Concerns over time have been preparation procedures, storage temperature, sterility, stability
and potency. The purpose of this study was to assess the stability and potency of 5% MAS over time and at varied
storage temperatures.
ATCC stock cultures of Pseudomonas aeruginosa (PSA), Escherichia coli, Enterobacter cloacae, Enterococcus faecalis,
Staphylococcus aureus (HAS), Methicillin Resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermis and
2 burn wound isolates of each species were tested for antimicrobial susceptibility/resistance and sterility over 16 weeks.
The antimicrobial activity was determined using the Holder Wet L disc Antimicrobial Solution Assay. Sterility was
confirmed by brother culture, and testing was done weekly. The antibiotic solution was prepared in the manner and
concentration used in clinical wound care and stored at 37, 25 and 4° C.
Sterility for all test solutions was maintained using standard laboratory sterile technique for the length of the study.
Antimicrobial activity varied from species to species and strain-to-strain, but individual strain sensitivity patterns remained
constant throughout the study. PSA, HAS, E. faecalis and MRSA and their burn isolates were all sensitive to MAS. S.
epidermidis and both burn isolates were resistant, and E. coli was resistant with one isolate resistant and one sensitive. E.
cloacae was sensitive with one isolate resistant and one sensitive to storage temperature. (Efficacy was unaffected by
storage temperature).
In conclusion, topical 5% MAS can be prepared in advance for use as a burn wound dressing; it can be stored in the
incubator, on the shelf, or in the refrigerator for at least 16 weeks. This is a cost effective way to use 5% mafenide acetate
suspension, which does not jeopardize sterility, stability, or potency.
(Proceedings American Burn Assoc. 1996:173.)
30
E) MOIST WOUND HEALING IN BURNS
(Experience with 5% Sulfamylon Solution)
Meshed Skin Graft
5 Days Later
Meshed Skin Graft
5 Days Later
Irrigation system to maintain surface moisture
plus antibacterial protection using catheters
31
Moist Wound Healing with Mid to Deep
Partial Thickness Burn (5% Sulfamylon Solution)
Mid-dermal chemical burn
Moist wound healing with Sulfamylon Solution
Complete re-epithelialization at 21 days
32
IV. R E F E R E N C E S
HISTORY OF WOUND & BURN CARE FROM EXPOSURE TO MOIST HEALING
Bryan CP: Ancient Egyptian Medicine: The papyrus Ebers. London, Ares. 1930.
Jones WHS, Withington ET: Hippocrates, vol. 4, Cambridge, MA. Harvard University Press 1923-1931.
Mettler CC: History of Medicine. Philadelphia, Blakiston, 1947.
Sonnenburg E, Tschmarke P: Die Verbrennungen und Die Erfrierungen. Stuttgart, 1915, p 618.
Dzondi KH: Ueber Verbrennungen und das Einzige. Sichere Mittel sie in Jedem Grade Schnell and Schmerzlos zu Heilen.
Halle, Hemmerde und Schwetschke, 1816, p 1-64.
Hebra FV. Ueber continierliche allgemeine bader und deren anwen-dung bei behandlung von verbrennungen. Allgemeine
Wiener Medizinische Zeitung 1861:6;351-352, 359-360.
Erichsen JE. On the pathology of burns. London Medical Gazette 1843:31;524-533, 588-593.
Copeland WP. The treatment of burns. The Medical Record (NY) 1887:31;518.
Sneve H. The treatment of burns and skin grafting. JAMA 1905:45;1-8.
John DS. The open air treatment of burns. Am J Surg 1910:24;255-256.
Artz CP: Historical aspects of burn management. Surg Clin North Am Dec 1970:50;6, 1193-1200.
Davidson EC. Tannic acid in the treatment of burns. Surg Gyn Obstet 1925:41;202.
Aldrich RH. Treatment of burns with a compound of aniline dyes. N Engl J Med 1937:217;911-914.
Moncrief J: The development of topical therapy. J Trauma 1971:11;906-910.
Fox CL: Topical therapy and the development of silver sulfadiazine. Surg Gynecol Obstet 1983:157;82-88.
MOIST WOUND HEALING (THE CONCEPT)
Winter G. Formation of the scab and rate of epithelialization of superficial wounds in the skin. Nature 1962:193;293.
Wheeland RG. Wound healing and the newer surgical dressings. In: Moschella St., Hurley HJ, et al, eds. Dermatology,
Philadelphia: WB Saunders 1992:2305-11.
Silverman RA, Lender J, Elmets CA. Effects of occlusive and semiocclusive dressings in the return of barrier function to
trans-epidermal water loss in standardized human wounds. J Am Acad Dermatology 1989:20;755-60.
Mertz PM, Eaglstein WH. The effect of a semiocclusive dressing on the microbial population in superficial wounds. Arch
Surgery 1984:119:287-9.
Katz MH, Alvarez AF, Kirsner RS, et al. Human wound fluid from acute wounds stimulates fibroblast and endothelial cell
growth. J Am Acad Dermatol 1991:25;1054-8.
33
Madden MR, Nolan E, Finkelstein JL, et al. Comparison of an occlusive and semi-occlusive dressing and the effect of the
wound exudate upon Keratinocyte proliferation. J Trauma 1989:29;924-31.
Kannon G, Garrett A. Most wound healing with occlusive dressings. Dermatol Surg 1995:21;583.
Field C, Kerstein M. Overview of wound healing in a moist environment. Am J Surg 1994:167;2.
Bolton L, Monte K, Pirone L. Moisture and healing: beyond the jargon. Ostomy/Wound Management 2000:46;51.
MOISTURE AND INFLAMMATION
Madden M, Nolan E, Finkelstein J. Comparison of an occlusive and semiocclusive dressing and the effect of the wound
exudate upon keratinocyte proliferation. J Trauma 1989:29;924.
Vogt P, et al. Dry, moist and wet skin wound repair. Ann Plast Surg 1995:34;493.
WOUND MOISTURE AND BACTERIAL GROWTH
Mertz P, Eaglstein W. The effect of a semiocclusive dressing on the microbial population in superficial wounds. Arch Surg
1984:119;287.
Brueing K, Eriksson E, et al. Healing of partial thickness wounds in a liquid environment. J Surg Res 1992:52;50.
Davies J. Synthetic materials for covering burn wounds: progress toward perfection. Part 1: Short term dressing material.
Burns 1984:10;94.
Deitch E, Bacter C. Failure of local immunity: a potential cause of burn wound sepsis. Arch Surg 1985:120;78.
Hutchinson J, McGuckin M. Occlusive dressings: microbiologic and clinical reviews. Am J Infect Control 1990:18;257.
WET WOUND DRESSING
Breuing KH, Eriksson E, Liu PY, Miller DR. Healing of partial thickness procine skin wounds in a liquid environment.
Journal of Surgical Research. 1992:52(1); 50-58.
Vogt PM, Breuing KH, Liu PY, Binder T, Eriksson E. Both wet and moist wound environments accelerate epithelialization.
In: Altmeyer et al (eds); Wound healing and skin physiology. Springer 1993.
Vogt PM, Andree C, Breuing KH, Liu PY, Slama J, Helo G, Eriksson E. Dry, moist and wet skin wound repair. Ann Plast
Surg 1995:34;493-500
BURN WOUND MANAGEMENT (OVERVIEW)
Moncrief J. Topical therapy of the burn wound: present status. Clin Pharmacol Ther 1969:10;439.
Artz C. Historical aspects of burn management. Surg Clin N Amer 1970:50;6.
Moncrief J. The development of topical therapy. J Trauma 1971:11;998.
34
Boswick J. The role of dressings in treating burn wounds. In: The art and science of burn care 1987: Aspen Pub, pg 53.
Park G. Burn wound dressings – a review. Biomed Med Dev 1978:6;1.
Salisbury R, Wilmore D. Biological dressing for skin graft donor site. Arch Surg 1973:100;705.
Tavis M, et al. Modified collagen membrane as a skin substitute. J Biomed Mater Res 1975:9;785.
Deitch E. Failure of local immunity: a potential cause of burn wound sepsis. Arch Surg 1985:120;78.
Zawacki B. Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg 1979:180;98.
PROPHYLACTIC TOPICAL ANTIBIOTICS IN BURNS
Monafo W. Bessey P. Wound care; In Total burn care. Editor D Herndon, Saunders 1997:, pg 88.
Monafo W. Current treatment recommendations for topical burn therapy. Drugs 1990:40;364.
Fox C et al. Topical chemotherapy for burns using cerium salts and silver sulfadiazine. Surg Gynec Obstet 1977:144;668.
Hagger J et al. Antimicrobial therapy in burn patients. Surg Rounds 1992:699.
Robson M. Bacterial control in the burn wound. Clin Plas Surg 1979:6:515.
CURRENT USE OF TOPICAL ANTIBIOTIC CREAM FOR TREATING BURN INFECTION
Moncreif J ET al. The use of a topical sulfonamide in the control of burn wound sepsis. J Trauma 1966:6;907.
Robson M. The use of topical agents to control bacteria in the burn wound. Dimick A editor 1977, pg 17.
Robson M. Burn sepsis. Crit Care Clinics 1988:4;281.
Lindberg R, et al. Control of experimental and clinical burn wound sepsis by topical application of sulfamylon compounds.
Ann NY Acad Sci 1998:150;950.
Fox C. Silver sulfadiazine: a new topical therapy for pseudomonas in burns. Arch Surg 1968:96;184.
EFFECT OF TOPICAL CREAMS ON HEALING
Boulton L. Topical agents and moist healing. Clin Dermat 1994:12;95.
Orgill D, Demling RH./ Current concepts and approaches to wound healing. Crit Care Med 1988:16;899-908.
Cooper ML, Boyce ST. Hansbrough JF, Foreman TJ, Frank DH. Cytotoxicity to cultured human keratinocytes of topical
antimicrobial agents. J Surg Res 1990:48;190195.
Linweaver H. Topical antimicrobiol toxicity. Arch Surg 1985:120;267.
35
Boyce ST, Warden GD, Holder IA. Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and
fibroblasts for cultured skin grafts. J Burn Care Rehab 1995:16:97-103.
Smoot EC, Kucan JO, Roth A, Mody N, Debs N. In vitro toxicity testing for antibacterials against human keratinocytes.
Plast Reconstr Surg 1991:87;917-924.
McCauley RL, Li YY, Poole B, Evans MJ, Robson MC, Heggers JP, Herndon DN. Differential inhibition of human basal
keratinocyte growth to silver sulfadiaine and mafenide acetate. J Surg Res 1992:52;276-285.
BACTERIAL GROWTH, AND SKIN GRAFTS SURVIVAL
Krizek T, Robson M, Bacterial growth and skin graft survival. Surg Forum 1967:18;516.
Bacchetta C, Magee W, Rodeheaver G, et al. Biology of infections of split thickness skin grafts. Am J Surg 1975:130;63.
Neely A, Childress C, Maley M, Holder. Causes of colonization of autografted burn wounds. J Burn Care Rehab
1991:12;299.
Robson M, Stenberg B, Heggers J. Wound healing alterations caused by infection. Clin Plast Surg 1990:17;485.
Holdor I, Boyce S. Formulation of idealized topical antimicrobial mixture for use with cultured skin grafts. J Antimicrob
Chemother 1996:38;457.
Livingston D, Cryer N, et al. A randomized prospective study of topical antibiotic agents on skin grafts after thermal injury.
J Plast Reconstr Surg 1998:19;105.
ANTIBACTERIAL SOLUTIONS AND MOIST HEALING IN BURNS (5% SULFAMYLON SOLUTION)
Maggi S, Soler P, Robson M. The efficacy of 5% sulfamylon solution for the treatment of contaminated explanted human
meshed skin grafts. Burns 1999:5;237.
Heinle E, Dougherty W, Garner W. The use of 5% mafenide acetate solution in the post-graft treatment of necrotizing
fasciitis. J Burn Care Rehab 2001:22; 35-42.
Shuck JM, Einfeldt LE, Trainor MP. Sulfamylon solution dressings in the management of burn wounds: Preliminary clinical
report. J Trauma 1972:12;999-1002.
Kucan JO, Smoot EC. Five percent mafenide acetate solution in the treatment of thermal injuries. J Burn Care Rehab
1993:144;158-163.
Harries RHC, Rogers BG, Leitch IOW, Robson MC. An in vivo model for epithelialization kinetics in human skin. Aust
N.Z.J. Surg 1995:65;600-3.
Lee JJ, Marvin JA, Heimbach DM, Grube BJ. Use of 5% sulfamylon (mafenide) solution after excision and grafting of
burns. J Burn Care Rehab 1988:9;602-5.
Mendelson J. Management of burns under condition of limited resources using topical aqueous sulfamylon spray. J Burn
Care Rehab 1997:18;258.
Hanson N, Shuck G. Studies of the pain produced by mafenide acetate preparation in burns. Arch Surg 1975:110;1446.
36
Currerri P, Shuck J, Pruitt B. Treatment of burn wounds with 5% aqueous sulfamylon and occlusive dressings. Surg
Forum 1970:20;506.
Lee J, Marvin J, Heimbach D. Use of 5% sulfamylon solution after excision and grafting in burns. J Burn Care Rehab
1988:9;602.
Harrison H, Bales N, Jacoby F. The absorption into burned skin of sulfamylon acetate from 5% aqueous solution. J
Trauma 1972:12;794.
Murphy R, Kucan J, Robson M, Higgers J. The effect of 5% mafenide acetate solution on bacterial control in rat burns. J
Trauma 1982:23;878.
37
Cutaneous wounds managed with moist healing using an occlusive dressing beginning in mid-20th century
Exposure Method
Click the Image to Enlarge
Surface desiccation results in impairment to rate of re-epithelialization and decreases all phases of healing
Moist Healing
Click the Image to Enlarge
Fluid layer on wound surface increases not only the rate of re-epithelialization, but all aspects of healing
38
B. THE BURN WOUND
Click the Image to Enlarge
Burn wound managed by exposure or open method. Note: Dry surface with wound desiccation. This approach is no
longer considered appropriate.
39
•
Click the Image to Enlarge
Characteristics of Healing on Wound:
Without Moisture Layer
•
•
Slower epithelial movement as enzyme debridement thru eschar required
Increased wound inflammation (exudate)
Click the Image to Enlarge
40
41
Click to Enlarge the Image
Click to Enlarge the Image
Click to Enlarge the Image
Click to Enlarge the Image
Mid to deep dermal burn
42